{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,25]],"date-time":"2026-10-25T12:24:02Z","timestamp":1792931042139,"version":"4.5.0"},"reference-count":37,"publisher":"American Chemical Society (ACS)","issue":"2","license":[{"start":{"date-parts":[[2020,3,23]],"date-time":"2020-03-23T00:00:00Z","timestamp":1584921600000},"content-version":"vor","delay-in-days":59,"URL":"https:\/\/pubs.acs.org\/page\/policy\/authorchoice_ccbyncnd_termsofuse.html"}],"funder":[{"DOI":"10.13039\/100007465","name":"Universitetet i Troms\u00f8","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/100007465","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100000925","name":"National Health and Medical Research Council","doi-asserted-by":"publisher","award":["1141234"],"award-info":[{"award-number":["1141234"]}],"id":[{"id":"10.13039\/501100000925","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001774","name":"University of Sydney","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100001774","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100007811","name":"Sydney Medical School Foundation","doi-asserted-by":"publisher","award":["NA"],"award-info":[{"award-number":["NA"]}],"id":[{"id":"10.13039\/501100007811","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2020,2,25]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:p>Quantum dots (QDs) are used for imaging and transport of therapeutics. Here we demonstrate rapid absorption across the small intestine and targeted delivery of QDs with bound materials to the liver sinusoidal endothelial cells (LSECs) or hepatocytes in vitro and in vivo following oral administration. QDs were radiolabeled with 3H-oleic acid, with a fluorescent tag or 14C-metformin placed within a drug binding site. Three different biopolymer shell coatings were compared (formaldehyde-treated serum albumin (FSA), gelatin, heparin). Passage across the small intestine into mesenteric veins is mediated by clathrin endocytosis and micropinocytosis. 60% of an oral dose of QDs was rapidly distributed to the liver within 30 min, and this increased to 85% with FSA biopolymer coating. Uptake into LSECs also increased 3-fold with FSA coating, while uptake into hepatocytes was increased from 40% to 85% with gelatin biopolymer coating. Localization of QDs to LSECs was confirmed with immunofluorescence and transmission electron microscopy. 85% of QDs were cleared within 24 h of administration. The bioavailability of 14C-metformin 2 h post-ingestion was increased 5-fold by conjugation with QD-FSA, while uptake of metformin into LSECs was improved 50-fold by using these QDs. Endocytosis of QDs by SK-Hep1 cells (an LSEC immortal cell line) was via clathrin- and caveolae-mediated pathways with QDs taken up into lysosomes. In conclusion, we have shown high specificity targeting of the LSEC or hepatocytes after oral administration of QDs coated with a biopolymer layer of FSA or gelatin, which improved the bioavailability and delivery of metformin to LSECs.<\/jats:p>","DOI":"10.1021\/acsnano.9b06071","type":"journal-article","created":{"date-parts":[[2020,1,24]],"date-time":"2020-01-24T09:10:19Z","timestamp":1579857019000},"page":"1492-1507","source":"Crossref","is-referenced-by-count":56,"title":["Rapid\nIntestinal Uptake and Targeted Delivery to the\nLiver Endothelium Using Orally Administered Silver Sulfide Quantum\nDots"],"prefix":"10.1021","volume":"14","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-9001-0602","authenticated-orcid":true,"given":"Nicholas J.","family":"Hunt","sequence":"first","affiliation":[{"name":"Concord Repatriation General Hospital , , , ,","place":["Concord, New South Wales, Australia, 2139"]},{"name":"Concord Repatriation General Hospital , , , ,","place":["Concord, New South Wales, Australia, 2139"]},{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]},{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Glen P.","family":"Lockwood","sequence":"additional","affiliation":[{"name":"Concord Repatriation General Hospital , , , ,","place":["Concord, New South Wales, Australia, 2139"]},{"name":"Concord Repatriation General Hospital , , , ,","place":["Concord, New South Wales, Australia, 2139"]},{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frank H.","family":"Le Couteur","sequence":"additional","affiliation":[{"name":"Concord Repatriation General Hospital , , , ,","place":["Concord, New South Wales, Australia, 2139"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter A. G.","family":"McCourt","sequence":"additional","affiliation":[{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]},{"name":"University of Troms\u00f8 - The Arctic University of Norway , , ,","place":["Troms\u00f8, Norway, 9037"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nidhi","family":"Singla","sequence":"additional","affiliation":[{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sun Woo Sophie","family":"Kang","sequence":"additional","affiliation":[{"name":"Concord Repatriation General Hospital , , , ,","place":["Concord, New South Wales, Australia, 2139"]},{"name":"Concord Repatriation General Hospital , , , ,","place":["Concord, New South Wales, Australia, 2139"]},{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Andrew","family":"Burgess","sequence":"additional","affiliation":[{"name":"Concord Repatriation General Hospital , , , ,","place":["Concord, New South Wales, Australia, 2139"]},{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Zdenka","family":"Kuncic","sequence":"additional","affiliation":[{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]},{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]},{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Le Couteur","sequence":"additional","affiliation":[{"name":"Concord Repatriation General Hospital , , , ,","place":["Concord, New South Wales, Australia, 2139"]},{"name":"Concord Repatriation General Hospital , , , ,","place":["Concord, New South Wales, Australia, 2139"]},{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]},{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6346-9928","authenticated-orcid":true,"given":"Victoria C.","family":"Cogger","sequence":"additional","affiliation":[{"name":"Concord Repatriation General Hospital , , , ,","place":["Concord, New South Wales, Australia, 2139"]},{"name":"Concord Repatriation General Hospital , , , ,","place":["Concord, New South Wales, Australia, 2139"]},{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]},{"name":"The University of Sydney , , , ,","place":["Sydney, New South Wales, Australia, 2006"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"316","published-online":{"date-parts":[[2020,1,24]]},"reference":[{"key":"2026090404255482100_cit1","doi-asserted-by":"publisher","first-page":"2016","DOI":"10.1126\/science.281.5385.2016","article-title":"Quantum Dot Bioconjugates\nfor Ultrasensitive Nonisotopic Detection","volume":"281","author":"Chan","year":"1998","journal-title":"Science"},{"key":"2026090404255482100_cit2","doi-asserted-by":"publisher","first-page":"2013","DOI":"10.1126\/science.281.5385.2013","article-title":"Semiconductor\nNanocrystals as Fluorescent Biological Labels","volume":"281","author":"Bruchez","year":"1998","journal-title":"Science"},{"key":"2026090404255482100_cit3","doi-asserted-by":"publisher","first-page":"1212","DOI":"10.1038\/nmat4718","article-title":"Mechanism of Hard-Nanomaterial Clearance by\nthe Liver","volume":"15","author":"Tsoi","year":"2016","journal-title":"Nat. Mater."},{"key":"2026090404255482100_cit4","doi-asserted-by":"publisher","first-page":"R1217","DOI":"10.1152\/ajpregu.00686.2011","article-title":"The Scavenger Endothelial Cell: A\nNew Player in Homeostasis and Immunity","volume":"303","author":"S\u00f8rensen","year":"2012","journal-title":"Am.\nJ. Physiol. Regul. Integr. Comp. Physiol."},{"key":"2026090404255482100_cit5","doi-asserted-by":"publisher","first-page":"10130","DOI":"10.1021\/acsnano.8b04947","article-title":"Dense and Dynamic Polyethylene\nGlycol Shells Cloak Nanoparticles from Uptake by Liver Endothelial\nCells for Long Blood Circulation","volume":"12","author":"Zhou","year":"2018","journal-title":"ACS Nano"},{"key":"2026090404255482100_cit6","doi-asserted-by":"publisher","first-page":"4410","DOI":"10.1021\/acsnano.8b09655","article-title":"Dexamethasone\nConjugation\nto Biodegradable Avidin-Nucleic-Acid-Nano-Assemblies Promotes Selective\nLiver Targeting and Improves Therapeutic Efficacy in an Autoimmune\nHepatitis Murine Model","volume":"13","author":"Violatto","year":"2019","journal-title":"ACS Nano"},{"key":"2026090404255482100_cit7","doi-asserted-by":"publisher","first-page":"574","DOI":"10.1038\/s41467-019-08538-x","article-title":"Immune Modulation\nof\nLiver Sinusoidal Endothelial Cells by Melittin Nanoparticles Suppresses\nLiver Metastasis","volume":"10","author":"Yu","year":"2019","journal-title":"Nat. Commun."},{"key":"2026090404255482100_cit8","doi-asserted-by":"publisher","first-page":"709","DOI":"10.1002\/ijc.31343","article-title":"Targeting Liver Sinusoidal\nEndothelial Cells with miR-20a-Loaded Nanoparticles Reduces Murine\nColon Cancer Metastasis to the Liver","volume":"143","author":"Marquez","year":"2018","journal-title":"Int. J.\nCancer"},{"key":"2026090404255482100_cit9","doi-asserted-by":"publisher","first-page":"353","DOI":"10.1021\/bc1003179","article-title":"A Versatile and Tunable Coating Strategy Allows Control\nof Nanocrystal Delivery to Cell Types in the Liver","volume":"22","author":"Cormode","year":"2011","journal-title":"Bioconjugate Chem."},{"key":"2026090404255482100_cit10","doi-asserted-by":"publisher","first-page":"1711","DOI":"10.1002\/smll.201402698","article-title":"Intravital Multiphoton Imaging of the Selective Uptake of Water-Dispersible\nQuantum Dots into Sinusoidal Liver Cells","volume":"11","author":"Liang","year":"2015","journal-title":"Small"},{"key":"2026090404255482100_cit11","doi-asserted-by":"publisher","first-page":"387","DOI":"10.1021\/acsnano.5b05066","article-title":"Short-and Long-Term\nTracking of Anionic Ultrasmall Nanoparticles in Kidney","volume":"10","author":"Liang","year":"2016","journal-title":"ACS Nano"},{"key":"2026090404255482100_cit12","doi-asserted-by":"publisher","first-page":"12234","DOI":"10.1021\/acs.chemrev.6b00290","article-title":"New Generation Cadmium-Free Quantum Dots for Biophotonics\nand Nanomedicine","volume":"116","author":"Xu","year":"2016","journal-title":"Chem. 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Drug Delivery Rev."},{"key":"2026090404255482100_cit21","doi-asserted-by":"publisher","first-page":"8893","DOI":"10.1021\/acsnano.8b04315","article-title":"Oral Nanoparticles\nExhibit Specific High-Efficiency Intestinal Uptake and Lymphatic Transport","volume":"12","author":"Kim","year":"2018","journal-title":"ACS Nano"},{"key":"2026090404255482100_cit22","doi-asserted-by":"publisher","first-page":"405","DOI":"10.1016\/j.actbio.2017.10.025","article-title":"Overcoming Multiple\nGastrointestinal Barriers by Bilayer Modified Hollow Mesoporous Silica\nNanocarriers","volume":"65","author":"Wang","year":"2018","journal-title":"Acta Biomater."},{"key":"2026090404255482100_cit23","doi-asserted-by":"publisher","first-page":"10417","DOI":"10.1021\/acsnano.7b05547","article-title":"Oral siRNA\nDelivery\nto Treat Colorectal Liver Metastases","volume":"11","author":"Kang","year":"2017","journal-title":"ACS Nano"},{"key":"2026090404255482100_cit24","doi-asserted-by":"publisher","first-page":"233","DOI":"10.1016\/j.bbamem.2015.11.022","article-title":"Small Molecule Pinocytosis\nand Clathrin-Dependent Endocytosis\nat the Intestinal Brush Border: Two Separate Pathways into the Enterocyte","volume":"1858","author":"Danielsen","year":"2016","journal-title":"Biochim. 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Pharm."},{"key":"2026090404255482100_cit30","doi-asserted-by":"publisher","first-page":"G137","DOI":"10.1152\/ajpgi.00069.2008","article-title":"The Response\nof Fenestrations, Actin,\nand Caveolin-1 to Vascular Endothelial Growth Factor in SK Hep1 Cells","volume":"295","author":"Cogger","year":"2008","journal-title":"Am. J. Physiol Gastrointest Liver Physiol"},{"key":"2026090404255482100_cit31","doi-asserted-by":"publisher","first-page":"7794","DOI":"10.1038\/s41598-017-08259-5","article-title":"Measurement of Caveolin-1 Densities\nin the Cell Membrane for Quantification of Caveolar Deformation after\nExposure to Hypotonic Membrane Tension","volume":"7","author":"Tachikawa","year":"2017","journal-title":"Sci.\nRep."},{"key":"2026090404255482100_cit32","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1042\/bj20031253","article-title":"Size-Dependent Internalization\nof Particles via the Pathways of Clathrin-and Caveolae-Mediated\nEndocytosis","volume":"377","author":"Rejman","year":"2004","journal-title":"Biochem. J."},{"key":"2026090404255482100_cit33","doi-asserted-by":"publisher","first-page":"212","DOI":"10.1016\/j.cbi.2018.06.032","article-title":"Effects of Silver Sulfide Quantum Dots Coated with\n2-Mercaptopropionic Acid on Genotoxic and Apoptotic Pathways In Vitro","volume":"291","author":"Ozkan Vardar","year":"2018","journal-title":"Chem.-Biol. Interact."},{"issue":"31","key":"2026090404255482100_cit34","doi-asserted-by":"publisher","first-page":"4944","DOI":"10.1002\/ejic.201600881","article-title":"Universal Approach\nto the Synthesis of Silver Sulfide\nin the Forms of Nanopowders, Quantum Dots, Core-Shell Nanoparticles,\nand Heteronanostructures","volume":"2016","author":"Sadovnikov","year":"2016","journal-title":"Eur. J. Inorg. Chem."},{"key":"2026090404255482100_cit35","doi-asserted-by":"publisher","first-page":"220","DOI":"10.1021\/nn5071183","article-title":"Tunable Ultrasmall\nVisible-to-Extended Near-Infrared Emitting Silver Sulfide Quantum\nDots for Integrin-Targeted Cancer Imaging","volume":"9","author":"Tang","year":"2015","journal-title":"ACS\nNano"},{"key":"2026090404255482100_cit36","doi-asserted-by":"publisher","first-page":"115","DOI":"10.1002\/jcp.1040700115","article-title":"Heterolysosome Formation\nin Mouse Liver","volume":"70","author":"Mego","year":"1967","journal-title":"J. Cell. Physiol."},{"key":"2026090404255482100_cit37","doi-asserted-by":"publisher","first-page":"160","DOI":"10.1016\/j.yexcr.2004.09.017","article-title":"Stabilin-1\nand Stabilin-2 are Both\nDirected into the Early Endocytic Pathway in Hepatic Sinusoidal Endothelium via Interactions with Clathrin\/AP-2, Independent of Ligand\nBinding","volume":"303","author":"Hansen","year":"2005","journal-title":"Exp. 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